Mutations in a number of Drosophila genes produce phenotypes of seizure sensitivity, including a lowered threshold to evoked electrophysiologically recorded seizure-like activity and "bang-sensitive" phenotypes. This report describes work done with the fly gene Ncc69, which is orthologous to several potassium-chloride cotransporters (SLC12A2, SLC12A1, SLC12A3) in human. Classical amorphic and loss-of-function alleles, RNAi-targeting constructs, and alleles caused by insertional mutagenesis have been generated for Dmel\Ncc69. The human SLC12A1 gene has been implicated in Bartter syndrome, type 1 (MIM:601678), a disease involving defective renal reabsorption of sodium chloride.
To date, none of the orthologous SLC12A1-3 human genes has been reported as implicated in a seizure- or epilepsy-related disorder by OMIM. A UAS-construct for wild-type Hsap\SLC12A2 has been introduced into flies. Partial heterologous rescue (functional complementation) has been demonstrated for the neuroanatomy defects observed for amorphic mutations of Dmel\Ncc69.
RNAi-effected loss-of-function of Dmel\Ncc69 in glia, but not neurons, causes seizure-sensitivity. Results with both Ncc69 and transgenic Hsap\SLC12A2 support a role for glial cell cation-chloride cotransporters in maintaining neural extracellular solute composition, pressure and volume.
[updated Mar. 2022 by FlyBase; FBrf0222196]
